Array Comparative Genomic Hybridization Analysis of a Conventional Chordoma and an Adjacent Benign Notochordal Tumor Shows No Direct Lineage Relationship
Yang D Lee, Valentina Nardi, Long P Le, Vikram Deshpande, Francis J Hornicek, Anthony J Iafrate, Gunnlaugur P Nielsen. Massachusetts General Hospital, Boston, MA
Background: Chordoma is a locally aggressive malignant intraosseous neoplasm with a potential for distant metastasis and with histologic features reminiscent of the embryonic notochord. Studies have revealed loss of tumor suppressors such as Rb, TSC1 and TSC2, CDKN2A/p16, CDKN2B/p15, PTEN and amplification of the transcription factor brachyury, often with recurring patterns of chromosomal losses (chromosome 1p, 3, 4, 9, 10, 13, and 14) and gains (chromosome 7). However, it is unclear whether these genetic alterations represent early or late changes in the pathogenic process. Benign notochordal cell tumors (BNCTs) is a well-demarcated, intramedullary, cohesive aggregates of large cells with adipocyte-like, vacuolated or eosinophilic cytoplasm. In contrast to chordoma, BNCTs lack the myxoidy extracellular matrix, have minimal cytologic and nuclear atypia and show no evidence of invasion. Multiple recent studies have demonstrated BNCTs in close proximity to the chordomas, leading to the hypothesis that the former gives rise to the latter. However, an autopsy series show that up to 20% of the general population harbor BNCT in their vertebral bodies, opening the possibility that coexisting BNCT and chordoma may be coincidental. To this end, we have profiled a conventional chordoma and its adjacent BNCT to understand the lineage relationship between the two lesions.
Design: DNA samples were extracted from formalin fixed paraffin embedded, EDTA-decalcified chordoma and an adjacent BNCT, then hybridized to normal genomic DNA from the same patient, followed by array comparative genomic hybridization (aCGH) analysis.
Results: Our previous study has demonstrated that a BNCT lacks the complex genomic alterations commonly found in a conventional chordoma. Our current study identified heterozygous deletions of the KLF6 (tumor suppressor), HNRNPA2B1 and the MALAT1 loci, in addition to Y-chromosome loss in the BNCT - changes that are not identified in the chordoma from the same patient. Conversely, the chordoma shows commonly observed changes including the loss of chromosome 1p, 3, 4, 10, 13, and gain of chromosome 7 - none of which are present in the adjacent BNCT.
Conclusions: Our data show that the analyzed BNCT cannot be a precursor lesion of the adjacent conventional chordoma. However, the possibility of other unidentified or non-preserved BNCT giving rise to the chordoma cannot be ruled out.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 8, Tuesday Afternoon